The overall objective of the proposed research is to provide information towards understanding the control of neuronal and CNS development. The specific aims address questions concerning the generation of spatial pattern in the very early CNS, the mechansims of the formation of specific neuronal connections during embryogenesis, the degree to which the morphogenesis of neurons depends upon transsynaptic stimulation and other extrinsic factors, and the mechanisms responsible for the re-establishment of functional connections by regenerating axons. A single pair of neurons, the Mauthner cells (M-cells) are present in the medulla of premetamorphic amphibians. Because the M-cell is striking in size ans distinctive in form, and its location is precisely defined, it is easily distinguished morphologically. Most importantly, the M-cell can be approached experimentally during many stages of development, and the results can be assayed with morphological, behavioral and physiological methods. Thus the amphibian CNS provides a unique system for the study of various aspects of neuronal development. For example, there is a regional organization of synaptic connections on the surface of the M-cell. Experiments that involve microsurgery on embryos have been designed to see whether this topographic specification is due to regional differences on the surface of the M-cell itself. Microsurgical techniques will be used in most of the studies and the light and electron microscopes will be used in the analysis of the results. Knowledge of the mechanisms governing neuronal and CNS development is requisite to the interpretation of certain forms of mental retardation and congenital neurological disorders.